ORCID Profile
0000-0003-2942-5937
Current Organisation
National Taiwan Ocean University
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Publisher: Springer Science and Business Media LLC
Date: 04-07-2023
Publisher: Springer Science and Business Media LLC
Date: 04-09-2018
DOI: 10.1038/S41598-018-31644-7
Abstract: A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Publisher: Springer Science and Business Media LLC
Date: 18-12-2017
DOI: 10.1038/S41598-017-17672-9
Abstract: Therapeutics are currently unavailable for Venezuelan equine encephalitis virus (VEEV), which elicits flu-like symptoms and encephalitis in humans, with an estimated 14% of cases resulting in neurological disease. Here we identify anti-VEEV agents using in silico structure-based-drug-design (SBDD) for the first time, characterising inhibitors that block recognition of VEEV capsid protein (C) by the host importin (IMP) α/β1 nuclear transport proteins. From an initial screen of 1.5 million compounds, followed by in silico refinement and screening for biological activity in vitro , we identified 21 hit compounds which inhibited IMPα/β1:C binding with IC 50 s as low as 5 µM. Four compounds were found to inhibit nuclear import of C in transfected cells, with one able to reduce VEEV replication at µM concentration, concomitant with reduced C nuclear accumulation in infected cells. Further, this compound was inactive against a mutant VEEV that lacks high affinity IMPα/β1:C interaction, supporting the mode of its antiviral action to be through inhibiting C nuclear localization. This successful application of SBDD paves the way for lead optimization for VEEV antivirals, and is an exciting prospect to identify inhibitors for the many other viral pathogens of significance that require IMPα/β1 in their infectious cycle.
Publisher: Research Square Platform LLC
Date: 16-11-2022
DOI: 10.21203/RS.3.RS-2247153/V1
Abstract: Leading professional health bodies have called for the wider adoption of Patient Reported Outcome Measures, such as quality of life, in research and clinical practice as a means for understanding why the global burden of depression continues to climb despite increased rates of treatment use. Here, we examined whether anhedonia – an often recalcitrant and impairing symptom of depression – along with its neural correlates, was associated with longitudinal changes in patient-reported quality of life among in iduals seeking treatment for mood disorders. We recruited 112 participants, including n = 80 in iduals with mood disorders (58 unipolar, 22 bipolar) and n = 32 healthy controls (63.4% female). We assessed anhedonia severity along with two electroencephalographic markers of neural reward responsiveness (scalp-level ‘Reward Positivity’ litude and source-localized reward-related activation in the dorsal anterior cingulate cortex), and assessed quality of life at baseline, 3- and 6-month follow-up. Anhedonia emerged as a robust correlate of quality of life cross-sectionally and longitudinally among in iduals with mood disorders. Furthermore, increased neural reward responsiveness at baseline was associated with greater improvements in quality of life over time, and this improvement was mediated by longitudinal improvements in anhedonia severity. Finally, differences in quality of life observed between in iduals with unipolar and bipolar mood disorders were mediated by differences in anhedonia severity. Our findings indicate that anhedonia and its reward-related neural correlates are linked to variability in quality of life over time in in iduals with mood disorders. Treatments capable of improving anhedonia and normalizing brain reward function may be necessary for improving broader health outcomes for in iduals seeking treatment for depression. ClinicalTrials.gov identifier: NCT01976975
Publisher: Research Square Platform LLC
Date: 28-09-2023
Location: United States of America
Location: United States of America
No related grants have been discovered for Shih-Chao Lin.